Differential effects of chaperones on yeast prions: CURrent view
Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions. Yeast prions, including the best studied ones ([PSI +] and [URE3]), propagate via intimate interactions with molecular chaperones. Different yeast prions exhibit differential responses to changes in levels, functionality or localization of the components of chaperone machinery. Here, we provide additional data confirming differential effects of chaperones (and specifically, Hsp40s) on yeast prions and summarize current knowledge of the mechanisms underlying chaperone specificities. Contrary to frequent statements in literature, overproduction of the Hsp104 chaperone antagonizes both [PSI +] and [URE3] prions, while overproduction of the Hsp70-Ssa1 chaperone antagonizes [URE3] prion only in some, but not in all strains. Recently, we demonstrated that the relocalization of a fraction of the Hsp40 chaperone Sis1 from the cytosol to the nucleus by the chaperone-sorting factor Cur1 exhibits opposite effects on [PSI +] and [URE3] prions. We suggest that the response of prions to changes in Sis1 localization represents a combination of the effects of Sis1 shortage on fragmentation of prion aggregates and on malpartition of prion aggregates during a cell division. Differences in sensitivity of prion fragmentation to Sis1 and in relative inputs of fragmentation and malpartition in prion propagation result in opposite effects of Sis1 relocalization on [PSI +] and [URE3].
KeywordsYeast prion Molecular chaperone Hsp40 Hsp70 Cur1
We thank Rebecca L. Howie and Gary P. Newnam for help in some experiments, Simon Alberti for the YAL-456 strain, and Varvara E. Tvorogova for the pGADT7-GW plasmid. This work was supported by St. Petersburg State University (projects 15.61.2218.2013, 1.37.291.2015, and 1.40.1327.2017) and grants from the Russian Foundation for Basic Research (16-04-00202, 15-04-00650 and 15-04-08159), Russian Science Foundation (14-50-00069), and National Science Foundation (MCB 1516872). Technical help was provided by Resource Centers “Development of Molecular and Cell Technologies” and “Biobank” of St. Petersburg State University.
- Barbitoff YA, Matveenko AG, Moskalenko SE, Zemlyanko OM, Newnam GP, Patel A, Chernova TA, Chernoff YO, Zhouravleva GA (2017) To CURe or not to CURe? Differential effects of the chaperone sorting factor Cur1 on yeast prions are mediated by the chaperone Sis1. Mol Microbiol 105:242–257. doi: 10.1111/mmi.13697 CrossRefPubMedGoogle Scholar
- Kiktev DA, Chernoff YO, Archipenko AV, Zhouravleva GA (2011) Identification of genes influencing synthetic lethality of genetic and epigenetic alterations in translation termination factors in yeast. Dokl Biochem Biophys 438:117–119. doi: 10.1134/S1607672911030021 CrossRefPubMedPubMedCentralGoogle Scholar
- Miller SB, Ho CT, Winkler J, Khokhrina M, Neuner A, Mohamed MY, Guilbride DL, Richter K, Lisby M, Schiebel E, Mogk A, Bukau B (2015) Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition. EMBO J 34:778–797. doi: 10.15252/embj.201489524 CrossRefPubMedPubMedCentralGoogle Scholar
- Sharma D, Martineau CN, Dall MT Le, Reidy M, Masison DC, Kabani M (2009) Function of SSA subfamily of Hsp70 within and across species varies widely in complementing Saccharomyces cerevisiae cell growth and prion propagation. PLoS ONE 4:e6644. doi: 10.1371/journal.pone.0006644 CrossRefPubMedPubMedCentralGoogle Scholar